Immunological analyses of human papillomavirus capsids

Recombinant human papillomavirus (HPV) virus-like particles (VLPs) are prom ising vaccine candidates for controlling anogenital HPV disease. Questions remain, however, concerning the extent of capsid antigenic similarity betwe en closely related virus genotypes. To investigate this issue, we produced VLPs and corresponding polyclonal immune sera from several anogenital HPV t ypes, and examined these reagents in enzyme-linked immunosorbent assays (EL ISAs) and in cross-neutralization studies. Despite varying degrees of L1 ge neric sequence relatedness, VLPs of each type examined induced high-titer s erum polyclonal antibody responses that were entirely genotype-specific. In an in vitro infectivity assay, only cognate VLP antisera were able to neut ralize pseudovirions of HPV-16, HPV-18 acid HPV-33, with two exceptions: HP V-31 and HPV-45 VLP post-immune sera demonstrated low levels of neutralizin g activity against pseudovirions of HPV-33 and HPV-18, respectively. In oth er experiments, epitopes shared between closely related types were found to be less immunogenic than. and antigenically distinct from, primary type-sp ecific B-cell determinants of the viral capsid. In addition, results from e pitope blocking experiments suggested a close correlation between primary t ype-specific capsid antigenic sites and virion neutralization. These findin gs support the view that papillomavirus genotypes denote unique viral serot ypes, and suggest that a successful vaccine for these viruses will likely r equire the inclusion of VLPs of each serotype for which protection is desir ed. (C) 2001 Elsevier Science Ltd. All rights reserved.